Severe Asthma Research Articles

Clinical Remission Predictors in Non-Colonized Bronchiectasis and Severe Asthma with Type 2-Targeted Biologic Therapy: A Retrospective Real-Life Pilot Study.

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population.

Increased expression of Cathepsin C in airway epithelia exacerbates airway remodeling in asthma.

Airway remodeling is a critical factor determining the pathogenesis and treatment sensitivity of severe asthma (SA) or uncontrolled asthma (UA). The activation of epithelial-mesenchymal trophic units (EMTUs) regulated by airway epithelial cells (AECs) has been proven to induce airway remodeling directly. However, the triggers for EMTU activation and the underlying mechanism of airway remodeling are not fully elucidated. Here, we screened the differentially expressed gene Cathepsin C (CTSC)/dipeptidyl peptidase 1 (DPP-1) in epithelia of SA and UA patients using RNA sequencing data and further verified the increased expression of CTSC in induced sputum of asthma patients which was positively correlated with the severity and airway remodeling. Moreover, direct instillation of exogenous CTSC induced airway remodeling. Genetic inhibition of CTSC suppressed EMTU activation and airway remodeling in two asthma models with airway remodeling. Mechanistically, increased secretion of CTSC from AECs induced EMTU activation through p38-mediated pathway, further inducing airway remodeling. Meanwhile, inhibition of CTSC also reduced the infiltration of inflammatory cells and the production of inflammatory factors in the lungs of asthmatic mice. Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA.

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

Prevalence and severity of asthma among school children in Hong Kong.

This study presents contemporary epidemiological data regarding the prevalence and severity of asthma and wheezing among children in Hong Kong, which provides an update to the results of the International Study of Asthma and Allergies in Childhood (ISAAC) conducted in 1994-1995 and 2001-2003. This cross-sectional investigation was based on the ISAAC study protocol. Responses from 1100 children aged 6 to 7 years (Primary 1-2) and 1048 children aged 13 to 14 years (Secondary 2-3) in Hong Kong between September 2020 and August 2021 were analysed. Sex differences within each age-group were assessed using Chi squared and independent t tests. Demographic information was entered into hierarchical logistic regression models to identify potential predictive factors associated with asthma severity. Annual change in prevalence was calculated via division of the prevalence by the number of years between surveys. Logistic regression modelling was conducted to identify risk factors associated with asthma severity. The prevalences of current wheezing were 6.19% and 4.97% in the primary and secondary school groups, respectively. The prevalences of asthma ever were 5.55% and 6.12%, whereas those of wheezing ever were 20.38% and 12.05%, in the primary and secondary school groups, respectively. Asthma severity and prevalence have decreased in Hong Kong since 1994-1995. A followup study will explore the protective and risk factors contributing to these trends.

Achieving clinical remission in asthma with mepolizumab: a subanalysis on vitamin D as a predictor of response

Objective Mepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response. Method We assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal polyps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias. Result Our results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control. Conclusion Mepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy.

Prevalence of asthma in Catalonia (Spain): a retrospective, large-scale population-based study.

Asthma epidemiology reports an estimated global prevalence of about 4.3-8.6% in adults, with last differences among geographical regions. This study analyses a more significant population of asthma patients (473,737 individuals).To study the prevalence of medical diagnosis of asthma, overall and by age, gender, and disease severity, as well as comorbidities and type 2 biomarkers, and undergo medical treatments of a retrospective population-based asthma cohort from Catalonia (Spain). Individuals with a diagnosis of asthma established by medical records at different healthcare levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, comorbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment. The overall diagnosed asthma prevalence in the population of Catalonia was 6.3%, where patients mainly had mild asthma (5.3%) and were significantly higher in females (6.8%) than males (5.7%). By age groups, asthma was more prevalent in boys and young men adults; however, being more prevalent in females above the age of 30y. The prevalence of severe asthma was 0.4%, 42.6% had uncontrolled asthma, and a high proportion (84.2%) were under systemic corticosteroid prescription. As expected, SABAs were the most prescribed drug (62.6%), followed by systemic corticosteroids (43.3%). More than half (53.8%) of patients showed type 2 inflammation. Asthma prevalence in Catalonia is similar to other areas studied in Spain, with a high prevalence in women and of T2 asthma.

CRP Levels and Vitamin D as Predictors of Asthma Control: A Data-Driven Approach

Background: Asthma is a chronic inflammatory disease of the airways characterized by episodic exacerbations and airflow obstruction. Elevated C-reactive protein (CRP) levels indicate systemic inflammation and are associated with increased disease severity in asthma. Additionally, vitamin D is thought to modulate immune responses and inflammation, potentially influencing asthma control. This study explores the relationships between CRP levels, vitamin D levels, and asthma control, as measured by the Asthma Control Test (ACT). Objectives: The primary objective of this study was to assess the correlation between CRP levels, vitamin D levels, and asthma control in adult patients with asthma. The study aimed to determine whether CRP and vitamin D could serve as predictive markers for asthma control. Methods: This single-center, prospective observational study enrolled 40 adult patients with confirmed asthma from the outpatient pulmonary clinic of ESIC Government Hospital, Guwahati, Assam, India. Asthma control was evaluated using the ACT, with scores categorized as well-controlled (ACT ≥ 20) or poorly controlled (ACT < 20). Serum CRP and vitamin D levels were measured using the ELISA method. Pearson’s correlation coefficient and ANOVA were employed to analyze the relationships between these variables. Results: The study found a moderate negative correlation between CRP levels and ACT scores (r = -0.58), indicating that higher CRP levels were associated with poorer asthma control. Patients with CRP levels greater than 10 mg/dL had significantly lower mean ACT scores compared to those with lower CRP levels. In contrast, a strong positive correlation was observed between vitamin D levels and ACT scores (r = 0.879), with higher vitamin D levels associated with better asthma control. The ANOVA test revealed significant differences in ACT scores across different vitamin D and CRP categories (p < 0.05). Conclusions: The study suggests that elevated CRP levels are indicative of poorer asthma control, while higher vitamin D levels are associated with better control of asthma. CRP and vitamin D levels may serve as valuable biomarkers for assessing asthma severity and guiding treatment strategies. However, the variability in response to vitamin D supplementation highlighted the need for personalized approaches to asthma management. Further research is required to confirm these findings and explore the underlying mechanisms.

Impact of biological therapies on clinical outcomes in patients with severe eosinophilic asthma with chronic rhinosinusitis: an observational study from Saudi Arabia

BackgroundWe aimed to study the impact of biological therapies in Saudi Arabia on patients with severe asthma (SA) combined with chronic rhinosinusitis (CRS) in terms of clinical outcomes.MethodsThis is a retrospective observational cohort research that was undertaken at the severe asthma clinics of the Armed Forces Hospital of the Southern Region (AFHSR) and King Khalid University Hospital, Abha, from March to September 2022 to delineate the effects of 3 biological therapies (dupilumab, benralizumab, and omalizumab) in adults with SA and concomitant CRS. Clinical outcomes assessed included asthma exacerbation frequency, hospitalization rates, use of oral corticosteroids (OCs), and the asthma control test (ACT) scores before and 1 year after biological therapies.ResultsEighty patients were enrolled, with a mean age of 46.68. There were 45 (56%) females and 35 (44%) males. There was a notifiable decrease in the frequency of exacerbations and hospitalization and in the number of patients who received OCs after 6 and 12 months of biological therapies compared to pre-biological therapies, respectively (p < 0.001 each), while there was a significant increase in the ACT scores at 6 and 12 months post-biological therapies, compared to pre-biological therapies, respectively (p < 0.001). These significant differences were maintained with all the 3 biologics used.ConclusionsResults from the first study from two large Saudi Arabian tertiary centers for patients with SA and CRS agree with and support those of worldwide real-life ones. One-year follow-up showed the effectiveness of the 3 drugs in terms of reduced frequency of asthma hospitalizations and exacerbations, the use of OCs, and improved ACT scores. Further prospective multicenter studies are warranted.

Exposure to respirable silica contributes to lower airway inflammation in asthmatic horses.

Respirable mineral particles can induce lower airway inflammation, but the role they play in asthma of horses is unknown. Respirable mineral particles, particularly respirable silica, are an overlooked determinant of chronic lung inflammation (asthma) in horses. Twenty-three horses from an equine hospital population: 11 moderately affected (MEA), 7 severely asthmatic (SEA), and 5 control horses free from respiratory clinical signs. Prospective observational study. The quantity and quality of mineral particles found in bronchoalveolar lavage fluid (BALF) were characterized, with particular attention to silica content. Polarized light microscopy performed on cytospin slides identified intracellular birefringent particles as silica. Spectrometry-based analysis performed on whole BALF determined total mineral and silica percentage and concentration. Group-related differences in BALF mineral and silica load were investigated as well as associations with BALF cytology. Intracellular birefringent particles were increased in SEA vs MEA (median [interquartile range, IQR]), 12 [7] vs 4 [5] particles/30 high power fields [hpf], respectively; P = .01) and vs controls (4 [2] particles/30 hpf; P = .02). Total mineral concentration in BALF was similar between the groups studied, whereas silica concentration and percentage were increased in SEA vs MEA (1758 [887] particles/mL and 20 [10]% vs 867 [662] particles/mL and 8 [6]%; P = .009 and P = .001) and control group (355 [330] particles/mL and 6 [3]%; P = .0003 and P = .002). Silica load in BALF was associated with BALF neutrophilia in MEA and SEA. Respirable silica is associated with neutrophilic lower airway inflammation in horses and might contribute to asthma development.

Relationship between Serum Vitamin D Levels and Asthma Control in Adult Patients

Asthma is a heterogeneous disease characterized by respiratory symptoms that vary both over time and in intensity, along with limited expiratory airflow. This heterogeneity is related to the patient's genetic and environmental phenotype. Vitamin D levels can affect the severity of asthma and the success of asthma treatment. Vitamin D can also influence the effectiveness of glucocorticoid therapy as an anti-inflammatory. This study aimed to determine the relationship between serum vitamin D levels and asthma control, severity, obstruction, and exacerbation levels. This research was a descriptive cross-sectional study on asthma patients at Wahidin Sudirohusodo Hospital and its network for the period October–December 2023. Each research subject had a venous blood sample taken and then checked vitamin D levels at the Hasanuddin University Teaching Hospital Research Laboratory. This research involved 72 research subjects. Most of the research subjects were female (61.1%), aged &lt;45 years (52.8%), worked as housewives (29.2%), had overweight BMI (33.3%), and had a history of atopy (59.7%). The degree of airway obstruction in the study subjects was mostly mild (66.7%) and the degree of severity was intermittent, persistent, and the degree of exacerbation in the same sample (33.3%). The results of the study showed a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations where p&lt;0.05. Also, it is found that a weakly positive connection (R: 0.2–0.4) between vitamin D levels and ACT, FEV1, FEV/FVC. There is a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations. There was a relationship between vitamin D levels and the degree of obstruction assessed by spirometry in this study.

Use of Targeted Biologic Therapies in Asthma: Current Practice in India

Asthma remains a significant public health issue in India, with a growing number of patients experiencing severe and uncontrolled forms of the disease. Targeted biologic therapies, including omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab, have emerged as advanced treatment options for patients with severe asthma, especially those with allergic or eosinophilic phenotypes. These therapies work by targeting specific immunological pathways involved in asthma pathogenesis, offering better symptom control and reducing exacerbation rates. However, the high cost of biologics, limited access, and inconsistent insurance coverage pose significant barriers to their widespread use in India. Despite these challenges, real-world data from Indian studies demonstrate promising clinical outcomes with biologic therapies in patients with difficult-to-treat asthma. This review examines the current landscape of biologic use in India, challenges related to cost and accessibility, and future prospects for integrating these treatments into routine asthma care, particularly through cost- reduction strategies and expanded healthcare coverage.

Impact of Dupilumab on Skin Surface Lipid-RNA Profile in Severe Asthmatic Patients.

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma.

Efficacy and safety of omalizumab combined with allergen immunotherapy in children with moderate to severe allergic asthma.

Omalizumab enables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Single-Cell Hypertrophy Promotes Contractile Function of Cultured Human Airway Smooth Muscle Cells via Piezo1 and YAP Auto-Regulation.

Severe asthma is characterized by increased cell volume (hypertrophy) and enhanced contractile function (hyperresponsiveness) of the airway smooth muscle cells (ASMCs). The causative relationship and underlying regulatory mechanisms between them, however, have remained unclear. Here, we manipulated the single-cell volume of in vitro cultured human ASMCs to increase from 2.7 to 5.2 and 8.2 × 103 μm3 as a simulated ASMC hypertrophy by culturing the cells on micropatterned rectangular substrates with a width of 25 μm and length from 50 to 100 and 200 μm, respectively. We found that as the cell volume increased, ASMCs exhibited a pro-contractile function with increased mRNA expression of contractile proteins, increased cell stiffness and traction force, and enhanced response to contractile stimulation. We also uncovered a concomitant increase in membrane tension and Piezo1 mRNA expression with increasing cell volume. Perhaps more importantly, we found that the enhanced contractile function due to cell volume increase was largely attenuated when membrane tension and Piezo1 mRNA expression were downregulated, and an auto-regulatory loop between Piezo1 and YAP mRNA expression was also involved in perpetuating the contractile function. These findings, thus, provide convincing evidence of a direct link between hypertrophy and enhanced contractile function of ASMCs that was mediated via Piezo1 mRNA expression, which may be specifically targeted as a novel therapeutic strategy to treat pulmonary diseases associated with ASMC hypertrophy such as severe asthma.

A systematic review on the use of sevoflurane in the management of status asthmaticus in adults

BackgroundTo conduct a systematic review looking into the use of sevoflurane in the management of status asthmaticus (SA) in adults.MethodsWe performed a systematic search on PubMed, EMBASE, and The Cochrane Library – CENTRAL through 23rd August 2023, restricting to studies reported in English. We included studies reporting use of sevoflurane in asthmatics beyond its use as an anaesthetic agent in surgeries i.e. in the emergency department (ED) and critical care setting, and focused on patient’s clinical parameters, ventilation pressures and weaning of invasive ventilation.ResultsA total of 13 publications fulfilled the inclusion criteria, comprising of 18 cases. All publications were of case reports/ series and conference abstracts, and no randomised trials were available. Most patients required intubation despite best medical management before sevoflurane administration, and high airway pressures and respiratory acidosis were apparent. There was significant heterogeneity regarding severity of asthma, treatment instituted, and the delivery, duration and concentration of sevoflurane administered. Many of the studies also did not quantify the changes in parameters pre- and post-sevoflurane. Sixteen patients experienced improvements in clinical status with sevoflurane administration—one required escalation to extracorporeal membrane oxygenation (ECMO), and another did not survive.ConclusionThe systematic review suggests sevoflurane can be a valuable treatment option in SA. As these cases are rare and heterogenous, further prospective case series are needed to support this.

Features of children with critical asthma hospitalized in a pediatric intensive care unit: Results from the ICU-3A study.

Despite improvements in long-term asthma treatment, an increasing number of children are being hospitalized in pediatric intensive care units (PICU) for asthma. The main objective of this study was to describe a recent cohort of children hospitalized in PICU for asthma to identify risk factors associated with a need for respiratory support, and multiple PICU stays. We conducted a retrospective cohort study in three PICUs in Paris (intensive care units 3A Study), using medical files of children hospitalized for asthma between February 2019 and October 2020. Need for respiratory support was defined by the need for high-flow nasal cannula or mechanical ventilation (MV) (either noninvasive [NIV] or invasive [IMV]). During the study period, 252 stays corresponding to 234 patients were analyzed. MV was required in 17.5% of stays, for significantly younger patients (2.37 vs. 4.18 years, p = 0.002). On multivariate analysis, a higher risk of progression to a need for respiratory support was found for children requiring magnesium sulfate or oxygen therapy ≥6 L/mn before PICU admission (RR 4.48; CI95% [1.85-10.89]; p = 0.001, and RR 2.86; CI95% [1.13-7.22]; p = 0.03, respectively), and those with atelectasis detected on chest radiography (RR 3.38; CI95% [1.43-8.00]; p < 0.01). Multiple PICU stays were associated with greater social deprivation (RR for French Deprivation Index 1.25; CI95% [1.03-1.51]; p = 0.03). Children experiencing social deprivation are at greater risk of multiple PICU stays for severe asthma. After transfer to PICU, children with chest radiograph detected atelectasis on admission are at higher risk of needing respiratory support.

Opportunities to rehabilitation of multimorbid patients with asthma and obesity

BACKGROUND: The challenges of rehabilitation and achieving asthma control in patients with multimorbid conditions remain relevant despite advances in asthma treatment. Improving therapeutic approaches requires not only the development of new drugs, but also the creation of comprehensive individualized rehabilitation programs. AIM: To develop complex rehabilitation programs for patients with asthma and multimorbid diseases (obesity, osteoarthritis) and assess their impact on asthma and comorbid conditions. MATERIALS AND METHODS: 70 patients with asthma and obesity were divided into two groups: a rehabilitation group and a control group. The study evaluated external respiration functions, quality of life using Asthma Quality of Life Questionnaire (standardized), asthma control with Asthma Control Questionnaire-5 (ACQ-5), multimorbid pathology with Cumulative Illness Rating Scale (CIRS), Lequesne index, exercise capacity via 6-minute walk test, physical activity using questionnaire ODA23+, and levels of interleukin-6, interleukin-4, tumor necrosis factor alpha, leptin. RESULTS: Both groups were comparable across all assessed parameters, with most participants presenting moderate to severe asthma. Physical activity levels were low to moderate. The CIRS index was 10.0 ± 1.1 in group 1 and 9.2 ± 1.1 in group 2 (p 0.05), while the Lequesne index was 9.70 ± 1.47 and 8.80 ± 1 (p = 0.3900), respectively. After rehabilitation program, the Lequesne index in the group 1 decreased by 2.37 ± 0.60 (р 0,05), which correlated with improved exercise tolerance (6-minute walk test) and increased physical activity by 6.57 ± 2.00 (р 0.05), and increased asthma control (with ACQ-5 decreasing by 0.74 ± 0.20 points; р 0.05) and quality of life with Asthma Quality of Life Questionnaire (standardized) 3.8 ± 0.4 to 4.5 ± 0.3 (р 0.05). In group 2, no significant changes were observed in the Lequesne index, physical activity, asthma control, or quality of life (p 0.05). Proinflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and leptin, decreased significantly in group 1, while the control group showed no significant changes. CONCLUSIONS: Multicomponent rehabilitation programs tailored to the individual characteristics of patients with multimorbid conditions contribute to better management of both asthma and comorbidities. Rehabilitation improves asthma control, quality of life, and exercise tolerance. It also helps to reduce pain syndrome, increase physical activity, and decrease proinflammatory cytokines and leptin levels.

Association between preterm birth and asthma and atopic dermatitis in preschool children: a nationwide population-based study

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28 weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28–36 weeks of GA), and 2,138,379 of full-term (FT) infants (> 37 weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6 years of age, early asthma as onset at < 2 years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6 years of age, early AD as onset at < 2 years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21–1.37 for severe asthma; OR 1.55, 95% CI 1.30–1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80–0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22–1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41–1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67–0.79) for the OP group and 0.88 (95% CI: 0.87–0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population.What is Known:•Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children.•Preterm birth was associated with an increased risk of asthma, but few large nationwide studies.•Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies.What is New:• Preterm children, especially born before 28 weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis.• Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma.• Preterm children are vulnerable to both early-onset and severe asthma.

Efficacy and safety of benralizumab

The purpose of the review is to analyze Russian and foreign literature sources on the effectiveness and safety of benralizumab in the treatment of moderate and severe bronchial asthma. Benralizumab is a humanized monoclonal antibody directed against the interleukin-5 receptor (IL-5R) subunit. Binding of benralizumab with the alpha chain of IL-5R leads to inhibition of hetero-oligomerization of alpha and beta subunits, thus preventing signal transduction and consequent proliferation of eosinophils and basophils and the cascade of events following it. Benralizumab significantly reduces annual asthma exacerbation rates and is well tolerated by patients with severe uncontrolled asthma. The efficacy and long-term adverse reactions of benralizumab therapy have not been sufficiently studied and require more detailed analysis.

Targeting the IL-5 pathway in eosinophilic asthma: A comparison of anti-IL-5 versus anti-IL-5 receptor agents.

Eosinophilic asthma is characterized by frequent exacerbations, poor symptom control and accelerated lung function decline. It is now recognized that the immune response underlying eosinophilic asthma involves a complex network of interconnected pathways from both the adaptive and innate immune systems. Within this response, interleukin-5 (IL-5) plays a central role in eosinophil differentiation, activation and survival and has emerged as a key target for therapies treating severe asthma. The monoclonal antibodies mepolizumab and reslizumab target the ligand IL-5, preventing its interaction with eosinophils; in contrast, benralizumab binds to the IL-5 receptor (IL-5R), preventing IL-5 from binding and leading to substantially greater eosinophil reduction by enhanced antibody-dependent cell-mediated cytotoxicity. Although no direct head-to-head clinical trials of asthma have been published to formally evaluate the clinical significance of these different therapeutic approaches, the potential benefits of partial versus complete eosinophil depletion continue to remain an important area of study and debate. Here, we review the existing real-world and clinical study data of anti-IL-5/anti-IL-5R therapies in severe eosinophilic asthma.